5-溴-4-氯噻吩并[2,3-d]嘧啶 | 814918-95-1

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: 5-溴-4-氯噻吩并[2,3-d]嘧啶
• 中文别名: 5-溴-4-氯噻吩并[2,3-D]嘧啶
• 英文名称: 5-bromo-4-chlorothieno[2,3-d]pyrimidine
• CAS: 814918-95-1
• 化学式: C₆H₂BrClN₂S
• 分子量: 249.518
• InChiKey: IKCKRHCJPVDELP-UHFFFAOYSA-N

物化性质

• 沸点：
  345.5±37.0 °C(Predicted)
• 密度：
  1.955±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-Bromo-4-chlorothieno[2,3-d]pyrimidine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 5-Bromo-4-chlorothieno[2,3-d]pyrimidine
CAS number: 814918-95-1

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C6H2BrClN2S
Molecular weight: 249.5

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride, hydrogen bromide, sulfur
oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

5-溴-4-氯噻吩并[2,3-D]嘧啶是一种嘧啶类衍生物，可用作有机中间体，由6-溴-4-氯噻吩并[2,3-d]嘧啶制备得到。

制备

通过在二异丙胺（1.1毫升，790毫克，7.8毫摩尔）无水四氢呋喃 (THF) 溶液中添加己烷中的2.5摩尔BuLi（3.0毫升，7.6毫摩尔），制备锂二异丙胺(LDA)。将溶液升温至0℃并保持10分钟，随后在-100℃下逐滴添加到冷却的6-溴-4-氯噻吩并[2,3-d]嘧啶（如WO 2003053446中所述制备）THF 溶液中。将该混合物在 -90至-100℃保持45分钟，然后用饱和NH4Cl水溶液骤冷。将混合物用乙酸乙酯 (30毫升) 稀释并用水、盐水洗涤，干燥(Na2SO4)，并蒸发溶剂以获得残余物。从乙醇水溶液中重结晶该残余物，并通过硅胶柱洗脱，最终得到900毫克的产物。再通过反相高压液相色谱法 (HPLC) 从蒸发过的再结晶滤液中进一步分离并纯化目标物质，获得200毫克产物，总收率为55%。

反应信息

• 作为反应物：
  描述：

  5-溴-4-氯噻吩并[2,3-d]嘧啶 在 异丙基氯化镁 、 碘 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 以96%的产率得到4-氯-5-碘噻吩并[2,3-D]嘧啶
  参考文献：
  名称：

  抑制 PIP4Kγ 可改善突变亨廷顿蛋白的病理作用

  摘要：

  亨廷顿病 (HD) 致病基因的发现促进了许多努力，以揭示降低突变亨廷顿蛋白 (mHtt) 水平并可能阻止 HD 相关神经系统缺陷出现的细胞途径。使用基于细胞的致病性亨廷顿蛋白表达模型，我们确定了一类通过选择性抑制脂质激酶 PIP4Kγ 来保护细胞的化合物。PIP4Kγ 的药理抑制或敲低可调节细胞内磷脂酰肌醇 (PI) 种类之间的平衡并增加基础自噬，从而减少人类患者成纤维细胞中 mHtt 蛋白的总量和神经元中的聚集体。在亨廷顿病的两个果蝇模型中，PIP4K 的基因敲低改善了神经元功能障碍和退化，分别使用运动表现和视网膜退化测定进行评估。总之，这些结果表明 PIP4Kγ 是一种可药用靶标，其抑制作用增强了生产性自噬和 mHtt 蛋白水解，揭示了治疗亨廷顿病和其他神经退行性疾病的有用药理学干预点。

  DOI：

  10.7554/elife.29123
• 作为产物：
  描述：

  6-溴-4-氯噻吩[2,3-D]嘧啶 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以67.1%的产率得到5-溴-4-氯噻吩并[2,3-d]嘧啶
  参考文献：
  名称：

  [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF TREATING OR PREVENTING NEURODEGENERATIVE DISEASES OR DISORDERS
  [FR] COMPOSÉS, COMPOSITIONS PHARMACEUTIQUES, ET PROCÉDÉS DE TRAITEMENT OU DE PRÉVENTION DE MALADIES OU DE TROUBLES NEURODÉGÉNÉRATIFS

  摘要：

  本申请公开了以下式（I）的化合物：其中R1、R2、X、Y和Z如本文所述，或其药学上可接受的盐，用于治疗或预防神经退行性疾病和障碍，如亨廷顿病。还公开了包括这些化合物或其药学上可接受的盐以及药学上可接受的载体的药物组合物，以及治疗或预防神经退行性疾病和障碍的方法。

  公开号：

  WO2012044993A1

文献信息

• Macrocyclic MCL-1 inhibitors and methods of use
  申请人：AbbVie Inc.

  公开号：US20190055264A1

  公开（公告）日：2019-02-21

  The present disclosure provides for compounds of Formula (I) wherein A 2 , A 3 , A 4 , A 6 , A 7 , A 8 , A 15 , R A , R 5 , R 9 , R 10A , R 10B , R 11 , R 12 , R 13 , R 14 , R 16 , W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

  本公开提供了Formula (I)的化合物，其中A2、A3、A4、A6、A7、A8、A15、RA、R5、R9、R10A、R10B、R11、R12、R13、R14、R16、W、X和Y具有规范中定义的任何值，以及其药学上可接受的盐，可用作治疗疾病和病况的药物，包括癌症。还提供了包含Formula (I)化合物的药物组合物。
• [EN] IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK<br/>[FR] DÉRIVÉS D'IMIDAZOLIDINONE COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

  公开号：WO2017046739A1

  公开（公告）日：2017-03-23

  The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及取代咪唑烷酮衍生物。具体而言，该发明涉及根据式I（I）中R1、R2、R3、R4、R5、R6、R7、X、Y1、Y2和Z所定义的化合物。该发明的化合物是PERK的抑制剂，可用于治疗癌症、癌前综合征、阿尔茨海默病、神经病性疼痛、脊髓损伤、创伤性脑损伤、缺血性中风、中风、帕金森病、糖尿病、代谢综合征、代谢紊乱、亨廷顿病、克雅氏病、致命性家族性失眠、格斯特曼-施特劳斯勒-谢因克症候群及相关朊蛋白病、肌萎缩侧索硬化、进行性核上性麻痹、心肌梗死、心血管疾病、炎症、器官纤维化、肝脏慢性和急性疾病、脂肪肝病、肝脂肪变性、肝纤维化、肺部慢性和急性疾病、肺纤维化、肾脏慢性和急性疾病、肾脏纤维化、慢性创伤性脑病（CTE）、神经退行性疾病、痴呆症、额颞叶痴呆症、tau蛋白病、皮克氏病、尼曼-皮克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、心律失常、器官移植以及器官移植用途中的运输。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• [EN] IRAK INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'IRAK ET LEURS UTILISATION
  申请人：NIMBUS IRIS INC

  公开号：WO2012097013A1

  公开（公告）日：2012-07-19

  The present invention relates to compounds and methods useful for inhibiting one or more interleukin-l receptor-associated kinases ("IRAK"). In some embodiments, a provided compound inhibits IRAK-1 and IRAK-4. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

  本发明涉及化合物和方法，用于抑制一个或多个白细胞介素-1受体相关激酶（"IRAK"）。在某些实施例中，所提供的化合物抑制IRAK-1和IRAK-4。该发明还提供了包括本发明化合物的药学上可接受的组合物，以及使用所述组合物治疗各种疾病的方法。
• Thieno- and furo - pyrimidines and pyridines, useful as potassium channel inhibitors
  申请人：XENTION LIMITED

  公开号：US20140371203A1

  公开（公告）日：2014-12-18

  The present invention provides compounds of formula (I): (Formula (I); wherein A, R 1 , R 2 , R 3 I , V, X, and Z are defined herein, which are potassium channel inhibitors. The invention further provides pharmaceutical compositions comprising the compounds of formula (I) and their use in therapy, in particular in treatment of diseases or conditions that are mediated by K ir 3.1 and/or K ir 3.4 or any heteromultimers thereof, or that require inhibition of K ir 3.1 and/or K ir 3.4 or any heteromultimers thereof.

  本发明提供了式(I)的化合物：（式(I)；其中A、R1、R2、R3I、V、X和Z在此处定义，这些化合物是钾通道抑制剂。该发明还提供了包括式(I)的化合物的药物组合物及其在治疗中的使用，特别是在治疗由K ir 3.1和/或K ir 3.4或其任何异源多聚体介导的疾病或症状，或需要抑制K ir 3.1和/或K ir 3.4或其任何异源多聚体的情况。
• [EN] ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS D'ECTONUCLÉOTIDES PYROPHOSPHATASES/PHOSPHODIESTÉRASES 1 (ENPP1) ET LEURS UTILISATIONS
  申请人：SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INST

  公开号：WO2021133915A1

  公开（公告）日：2021-07-01

  Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  本文提供了外胞核苷酸焦磷酸酶/磷酸二酯酶1（ENPP1）的小分子调节剂，包括这些化合物的组合物，以及使用这些化合物和包含这些化合物的组合物的方法。